Electrical Stimulation Attenuates Muscle Atrophy Induced by Brachial Plexus Injury by Upregulating HO-1 Expression in Rats.

Abstract

In cases of global brachial plexus injury, long-term denervation results in severe muscle atrophy in the hand. This study was conducted to investigate the protective effect of electrical stimulation (ES) on denervated intrinsic forepaw muscle (IFM) induced by global brachial plexus avulsion (GBPA) in rats, and whether heme oxygenase-1 (HO-1) is involved in the effect of ES on denervated IFM atrophy. The authors established a GBPA rat model and denervated IFM was electrically stimulated at different frequencies (2, 10, and 20 Hz). Muscle fiber cross-sectional area, capillary supply, and muscular HO-1 protein level were measured. In addition, the expression of HO-1 was locally blocked by injecting the small interfering (si) RNA into IFM to determine the possible role of HO-1 in ES antiatrophic effect. Several key regulators of muscle protein synthesis and degradation were determined. All the stimulation protocols were able to ameliorate muscle capillary loss after denervation. ES at 20 Hz significantly attenuated denervated IFM atrophy. The protective effects of ES were markedly weakened by local injection of the HO-1 siRNA. Meanwhile, the expressions of MuRF-1, MAFbx, BNIP3, and the LC3B-II/I ratio were upregulated by denervation, whereas ES treatment attenuated the increment. Low muscular HO-1 level almost completely suppressed the ability of ES to inhibit the hydrolysis activity of autophagy-lysosomal pathway. ES at 20 Hz, using a clinically translatable protocol, is recommended to delay denervated IFM atrophy. Activation of HO-1 is an important mechanism involved in the protective effects of ES against denervation-related muscle atrophy. Muscular HO-1 may be a potential molecular marker for the instruction and optimization of stimulus settings. Muscle-targeted upregulation of HO-1 may be a promising strategy for retarding denervation-related muscle atrophy.